Heart disease remains the leading cause of morbidity and mortality in the United States, responsible for over 1,400,000 deaths in 2001. Limitations in technology have hampered our ability to ameliorate the impact of an important group of cardiac disorders, congenital heart disease. The multi-disciplinary project described in this five-year proposal will develop and validate new investigative and diagnostic technologies based on the emerging imaging technique, optical coherence tomography (OCT). OCT is capable of simultaneous imaging of structure and function in small biological samples with micrometer-scale resolution in vivo and in real time, and is potentially capable of measuring electromechanical events. A multi-disciplinary approach is necessary to target the development of these new tools for the purpose of improving our understanding of the mechanisms of congenital heart disease. Specific Aim 1: Develop and demonstrate OCT imaging technologies for developmental cardiology research applications and disseminate to collaborators for validation and baseline studies. Specific Aim 2: Develop and demonstrate image analysis and visualization methods and disseminate to collaborators for validation and baseline studies. Specific Aim 3: Validate and apply OCT technologies to investigations of normal and abnormal cardiac morphogenesis in the chick embryo. Longitudinal analysis. Specific Aim 4: Validate and apply OCT technologies to screen and analyze cardiac defects in genetically altered mouse lines. Analysis of conotruncal and ventricular wall abnormalities. The goal of this project is to develop and validate a novel set of tools that will combine structural and physiologic information at heretofore unachievable resolution scales for better insight into the mechanisms of normal and abnormal cardiac morphogenesis. The utility of these tools to enable experiments that were previously not possible will be established by baseline studies of chick and mouse models of normal and abnormal cardiac morphogenesis.